The development of effective strategies to prevent and treat HIV infection is of paramount importance to improve global human health. Simian immunodeficiency virus (SIV) infection of rhesus macaques (Macaca mulatta) is the most effective pre-clinical model of HIV infection. Members of the Macaca genus, however, harbor several viruses that could confound experimental results from studies relating to the AIDS prevention or cure. It is therefore vital to ensure a constant supply of specific pathogen free (SPF) rhesus macaques for experimental studies in AIDS research. Since 2002, the SPF Rhesus macaque breeding groups at Yerkes National Primate Research Center (YNPRC) have, in part, been supported by U24 funding. By the end of 2013, all breeding groups will be free of SIV, Simian T-Lymphotropic Virus (STLV), Simian Type D Retroviruses (SRV), and Herpes Simian B Virus (Herpes-B). The central aim of this final phase of U24 funding is to achieve financial sustainability for those U24-supported groups and to expand multi-generational, genetically characterized breeding groups to provide appropriately aged experimental animals for NIH funded AIDS research. To achieve this aim, proven management practices will be employed that allow optimum production of animals in socially stable breeding groups to provide animals to AIDS-related studies. A second aim of this project is to expand methodology for SRV and Herpes testing in the Yerkes Virology Core. On-site SRV and Herpes B testing will save costs and allow a more rapid colony management response should the virus status of any SPF animal be questionable. A third aim of this renewal is to transition to a more cost-effective, therefore financially sustainable, SNP-based and direct sequencing approach for macaque genotyping, providing AIDS investigators with pedigreed animals with confirmed sets of major histocompatibility complex (MHC). It is expected that the YNPRC SPF rhesus macaque breeding colony will be financially sustainable by the end of the next U24 funding period and will be recognized as a national resource of genetically well-characterized rhesus macaques available for HIV/AIDS research.